Human cancer-prone genetic diseases are being studied in order to identify groups of people with an increased susceptibility to environmental carcinogenesis. We are attempting to determine the clinical consequences as well as the molecular basis of their cellular hypersensitivity. Patients with xeroderma pigmentosum (XP) and ataxia telangiectasia, diseases with ultraviolet and X-ray sensitivity, respectively, and with familial malignant melanoma (dysplastic nevus syndrome) and neurofibromatosis, diseases with no documented environmental sensitivity, are being studied. Detailed examinations of the clinical features of affected individuals are being made. A registry of XP patients is being established. Cultures of skin and blood are being established and the effects on cell survival, DNA repair, and chromosome abnormalities after treatment with DNA damaging agents (ultraviolet, bleomycin, or psoralen plus long wavelength ultraviolet) are being examined. These studies may identify persons with increased risk of cancer and suggest modes of cancer prophylaxis. In addition, these diseases serve as models for studies of human environmental carcinogenesis.